Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux.

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7-10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3-5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis.

Nutrition in Children With Chronic Kidney Disease: How to Thrive?

The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.

Assessment of Dietary Phosphorus Intake and Implementation of Parental Phosphate Education in Pediatric Chronic Kidney Disease.

Introduction: Management of dietary phosphorus intake is a challenge in children with chronic kidney disease and is governed by regional food sources and culinary practices. The aim of this study was to evaluate dietary intake of phosphorus in these children and assess the utility of parental phosphate education for control of hyperphosphatemia. Methods: This prospective study included children aged 2-18 years with CKD stages 2-5D. Phosphorus intake was assessed by 24-hour dietary recall, analyzed using food processor software, and interpreted based on dietary reference intake (DRI) and suggested dietary intake (SDI). Parents of those with hyperphosphatemia were subjected to a structured phosphate education, and serum phosphate was monitored every 2 months for 6 months. Results: Seventy children were recruited (mean age 9.4 ± 3.4 years, CKD5/5D: 51% (n = 36)) with median duration of CKD being 3.8 (IQR2,6) years. In the overall cohort, 50% (35/70) had phosphorus intake exceeding DRI with no significant difference between groups [CKD 5/5D,52.7% (n = 19) vs CKD2-4 47% (n = 16), P = 0.63]. Mean daily phosphorus intake was comparable between children with and without hyperphosphatemia [908 ± 279 mg vs 814 ± 302 mg, P = 0.1]. Based on DRI, 44% of children with normal serum phosphate and 58% with hyperphosphatemia had increased dietary intake of phosphorus (P = 0.15). Based on SDI, 26% with normal serum phosphate and 94% with hyperphosphatemia had increased dietary phosphorus intake (P < 0.001). Hyperphosphatemia was observed in 51% (CKD 2-4); 33% CKD5-5D 66%, P = 0.6). Among 29 children completing 6 months of follow up, there was a significant reduction in mean serum phosphate levels (P = 0.001) which was independent of age, stage of CKD or intake of phosphate binders. At end of the study, hyperphosphatemia persisted in 34%. Conclusion: Compared to DRI, dietary assessment of phosphorus intake based on SDI was significantly associated with hyperphosphatemia in children with CKD 2-5D. In the majority, repeated parental structured phosphate education over 6 months was useful in managing hyperphosphatemia.

Antenatal urolithiasis: A case report.

Introduction: Although pediatric urolithiasis is an established entity, its antenatal diagnosis is rare. We hereby report a case detected at 20 weeks gestation and discuss the etiopathogenesis, predisposition, and surveillance following intervention. Case report: A 2-year-old girl with left renal pelvic calculus detected antenatally at 20 weeks was evaluated. Left hydronephrosis, obstructive pelvic calculus with a decrease in differential renal function on ethylene dicysteine (EC) renogram was confirmed. The metabolic workup was normal. Following stone extraction by left pyelolithotomy, a left ureteropelvic junction obstruction secondary to a mucosal valve was apparent which was excised and left pyeloplasty was done. Stone analysis revealed 100% cystine. Differential renal function and drainage improved post-surgery. The child, however, did not have a follow-up in the interim and presented with a recurrent stone one and a half years later. Conclusion: Knowledge of antenatal urolithiasis ensures continued follow-up, evaluation for metabolic disorders, and associated structural defects, especially with increasing stone size and increasing hydronephrosis. This helps in timely intervention and continued surveillance.

Clinical profile and outcome of arteriovenous fistulae in children on maintenance hemodialysis from a low-resource setting.

INTRODUCTION: Arteriovenous fistula (AVF) is the recommended access of choice in children on maintenance hemodialysis. The challenges of creating and maintaining a fistula in children are many. The objective of our study was to describe the clinical profile and outcomes of AVFs in children from a resource-limited setting. METHODS: A retrospective analysis of children who have had an AVF for maintenance hemodialysis from 2010 to 2020 was performed. The center protocol for creation and management of complications was followed. Failure of fistula to mature was defined as primary failure. Primary patency was defined as the time from creation of access to the first complication requiring intervention. The primary failure rate, duration of primary patency and associated risk factors, and 1- and 3-year primary fistula patency rates were studied. RESULTS: Thirty-six children (38 AVFs) with the median (interquartile range) age of 11 (8, 13) years were included. Brachiocephalic anastomosis was the most common site (75%) of AVF. The primary failure rate was 5.5% (2 of 36). The mean (95% confidence interval) duration of primary patency was 42.3 (29.9, 54.7) months. There were no particular factors associated with the duration of primary patency. The 1- and 3-year primary patency rate was 91% and 73%, respectively. CONCLUSIONS: In resource-limited settings, AVF had good primary patency and is a feasible and durable access for maintenance hemodialysis in children.

Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) cover a spectrum of structural malformations that result from aberrant morphogenesis of kidney and urinary tract. It is the most prevalent cause of kidney failure in children. Hence, it is important from a clinical perspective to unravel the molecular etiology of kidney and urinary tract malformations. Causal variants in genes that direct various stages of development of kidney and urinary tract in fetal life have been identified in 5-20% of CAKUT patients from Western countries. Recent advances in next generation sequencing technology and decreasing cost offer the opportunity to characterize the genetic profile of CAKUT in Indian population and facilitate integration of genetic diagnostics in care of children with CAKUT. METHODS: Customized targeted panel sequencing was performed to identify pathogenic variants in 31 genes known to cause human CAKUT in 69 south Indian children with CAKUT. The NGS data was filtered using standardized pipeline and the variants were classified using ACMG criteria. Genotype and phenotype correlations were performed. RESULTS: The cohort consisted of children mostly with posterior urethral valve (PUV) (39.1%), vesico-ureteric reflux (VUR) (33.3%) and multi-cystic dysplastic kidney (MCDK) (7.2%). No pathogenic or likely pathogenic variants were identified in the study. Most of our variants (n = 39, 60%) were variants of unknown significance with 25.6% (10/39) of them were identified as potentially damaging but were novel variants. CONCLUSIONS: The present study did not identify any disease-causing monogenic variants in the cohort. The absence of genetic cause may be due to limitations of panel-based testing and also due to higher proportion of children with abnormalities in lower urinary tract than hypodysplasia of kidneys. Clinical, larger targeted panel or whole exome sequencing may be a better method to characterize the genetic profile of Indians patients with CAKUT.

Protein Energy Wasting in Children With Chronic Kidney Disease and End-Stage Kidney Disease: An Observational Study.

OBJECTIVES: Protein energy wasting (PEW), a specific nutritional comorbidity associated with increased mortality, is underrecognized in children with chronic kidney disease (CKD). The aim of this study was to determine the burden and factors associated with PEW and assess the utility of parameters used to diagnose PEW in children with CKD and End stage kidney disease (ESKD). METHODS: Children between 2 and 18 years of age with CKD stages 2-5 were recruited over 30 months. Parameters of PEW assessed included body mass index for height, mid-upper arm circumference, height for age, appetite, serum albumin, cholesterol, transferrin, and C-reactive protein. Based on number of criteria fulfilled in each subject, PEW was further stratified as mild, standard, and modified PEW. RESULTS: One hundred twenty-three children (male:female 3:1, 73 in CKD stages 2-4, 50 with ESKD) were recruited. PEW was observed in 58% (47% in CKD stages 2-4 vs. 73% ESKD, P = .035). Longer duration and severity of disease was associated PEW. Reduced appetite (P = .001, P = .04), low mid-upper arm circumference (P = .000, P = .006), and low body mass index for height (P = .000, P = .007) were useful criteria to diagnose PEW in CKD stages 2-4 and ESKD, while most children did not meet biochemical criteria. Inflammation observed in 47% was higher in those with ESKD [CKD stages 2-4: 72 (39%) vs. ESKD: 29 (59%), P = .02] but was associated with PEW only in CKD stages 2-4. CONCLUSION: PEW was highly prevalent in children with CKD and ESKD. Appetite and anthropometry measures were more useful than biochemical criteria for diagnosis of PEW. Whereas inflammation was common, it was associated with PEW only in CKD stages 2-4. Pediatric CKD and ESKD may need exclusive diagnostic criteria for PEW based on anthropometry, appetite, and inflammation.

Approach to Diagnosis and Management of Hematuria.

Hematuria is one of the alarming manifestations of a renal disease. It can present as macroscopic hematuria or microscopic hematuria due to either glomerular or non-glomerular disorders. Clinical presentation and urine microscopy can differentiate glomerular from non-glomerular hematuria. In the majority, a good clinical examination and basic investigations including a urine microscopic examination with sophisticated tools like phase contrast and automated microscopes can help differentiate glomerular from non-glomerular causes for hematuria. Drug induced hematuria, especially secondary to use of analgesics needs to be recognized in routine clinical practice. Rarer causes of hematuria may need more detailed evaluation with a renal biopsy, electron microscopy, urine biochemical testing and imaging. There is no specific treatment to resolve or prevent hematuria. Resolution of hematuria usually occurs with appropriate management of the underlying disorder. Persistent microscopic hematuria indicates the presence of a renal disease that warrants close monitoring and evaluation. Prompt referral to a pediatric nephrologist is indicated in situations when hematuria does not resolve within 2 weeks of onset of glomerulonephritis, there is a need for a renal biopsy, in the presence of persistent microscopic hematuria and need for specific urine biochemistry testing or imaging studies.

Neonatal Acute Kidney Injury: A Survey of Perceptions and Management Strategies Amongst Pediatricians and Neonatologists.

Background: Neonatal Acute Kidney Injury (AKI) occurs in 40-70% of critically ill newborn infants and is independently associated with increased morbidity and mortality. Understanding the practice patterns of physicians (neonatologists and pediatricians), caring for neonates in India is important to optimize care and outcomes in neonatal AKI. Aim: The aim of this study was to identify differences in physician's perception and practice variations of diagnosis, management, and follow-up of newborn infants with AKI in India. Methods: An online survey of neonatologists and pediatricians in India caring for newborn infants with AKI. Results: Out of 800 correspondents, 257 (135 neonatologists and 122 pediatricians) completed the survey, response rate being 32.1%. Resources available to the respondents included level III NICU (59%), neonatal surgery (60%), dialysis (11%), and extracorporeal membrane oxygenation (ECMO, 3%). Most respondents underestimated the risk of AKI due to various risk factors such as prematurity, asphyxia, sepsis, cardiac surgery, and medications. Less than half the respondents were aware of the AKIN or KDIGO criteria, which are the current standard criteria for defining neonatal AKI. Only half of the respondents were aware of the risk of CKD in preterm neonates and nearly half were unaware of the need to follow up with a pediatric nephrologist. Conclusions: Similar to other regions worldwide, there exists a knowledge gap in early recognition, optimal management and follow up of newborn infants with AKI amongst Indian physicians.

Proteinuria in children with juvenile idiopathic arthritis: Making the case for early urinary screening.

Systemic onset juvenile idiopathic arthritis (SOJIA) can be associated with proteinuria due to various renal pathologies. We report two pediatric cases with SOJIA and nephrotic syndrome secondary to renal amyloidosis, a very rare complication in children. Once present, amyloidosis heralds a poor prognosis for the patient, though early detection may allow some improvement if the inflammatory arthritis is controlled.

Renal artery stenting in a 2-year-old child with resistant hypertension and neurofibromatosis.

The occurrence of vascular lesions in neurofibromatosis is uncommon but well documented. These vascular lesions when present, occur predominantly in the kidneys, endocrine glands, heart and gastrointestinal tract, causing stenosis or obliteration of the lumen. We report a case of uncontrolled resistant hypertension in a 2-year-old child presenting with neurofibromatosis who was found to have a high-grade ostial left renal artery stenosis and obliteration of the right renal artery. As the right kidney was small and hypo-functioning, and its renal artery was totally occluded, we subjected the child to a left renal angioplasty and bailout stenting. Following stenting, the blood pressure decreased with anti-hypertensive treatment. Based on a review of the literature, and to the best of our knowledge, this is the youngest child to have undergone renal artery stenting.

Detecting reflux: does ureteric jet Doppler waveform have a role?

BACKGROUND: Vesicoureteral reflux (VUR) has a prevalence of 30-40 % post-febrile urinary tract infection (UTI). If not detected early and treated, renal scarring, hypertension, and renal failure may occur. Micturating cystourethrography (MCU) is an invasive procedure associated with radiation exposure. Hence, this study aimed at evaluating the utility of ureteric jet Doppler waveform (UJDW) as a screening tool in detecting VUR, and at assessing the feasibility of performing it in children aged 2-4 years. METHODS: Any child 2-18 years old who needed an MCU was included. Exclusion criteria were active UTI, indwelling catheter, and inability to drink the required amount of fluid. The UJDW was performed prior to the MCU. RESULTS: One hundred eighty-two ureteric units were analyzed. Sensitivity and specificity of UJDW in detecting VUR was 80.3 and 87.9 %. Twenty-three children (45 ureteric units), aged 2-4 years were compared with 73 children (137 ureteric units), aged 5-18 years. Sensitivity and specificity of UJDW in detecting VUR in 2-4 years was 77.3 and 91.3 %, respectively; while in children ≥5 years, it was 81.8 and 87.1 %, respectively. CONCLUSIONS: UJDW has a uniformly high specificity regardless of age or etiological groups, making it a good tool for follow-up. UJDW is a feasible technique, even in children aged 2-4 years.

Effects of maternal vitamin A status on kidney development: a pilot study.

Nephron endowment ranges widely in normal human populations. Recent autopsy studies have drawn attention to the possibility that subtle congenital nephron deficits may be associated with increased risk of developing hypertension later in life. Since modest maternal vitamin A deficiency reduces nephron number in rats, we designed a pilot study to determine the prevalence of maternal vitamin A deficiency in Montreal (Canada) and Bangalore (India) and the usefulness of newborn renal volume as a surrogate for nephron endowment. Among 48 pregnant Montreal women, two (4%) had one isolated mid-gestation retinol level slightly below the accepted limit of normal (0.9 mumol/L), whereas 25 (55%) of 46 pregnant women in Bangalore had at least one sample below this limit. Average estimated retinoid intake was correlated with mean serum retinol in pregnant women from Bangalore. In Montreal where maternal vitamin A deficiency was negligible, we found that newborn renal volume (estimated by renal ultrasonography at 2-6 weeks of age) was correlated with surface area at birth and was inversely correlated with serum creatinine at 1 month. Interestingly, renal volume adjusted for body surface area in Montreal (184+/-44 ml/m(2)) was significantly greater than in Bangalore (114+/-33 ml/m(2)) (p<0.01). Definitive studies are needed to establish whether maternal vitamin A deficiency accounts for subtle renal hypoplasia in Indian newborns. If so, there may be important public health implications for regions of the world where maternal vitamin A deficiency is prevalent.

Cyclosporine in steroid dependent and resistant childhood nephrotic syndrome.

OBJECTIVE: To evaluate the efficacy of cyclosporine (CyA) monotherapy in steroid resistant (SRNS) and steroid dependent (SDNS) nephrotic syndrome in children. DESIGN: A retrospective study. SETTING: Tertiary kidney care center for children at Bangalore. METHODS: Forty-one children with SDNS and SRNS with normal renal functions were treated with CyA at a dose of 6 mg/kg/day initially and maintained at 3 to 4 mg/kg/day if remission was sustained. The dosage was adjusted according to the CyA blood levels in non-responders. RESULTS: The median age of patients was 93 months (range 48-936) months. Thirteen children had minimal change disease (MCNS), 10 had mesangial proliferative glomerulonephritis (GN). Ten had membrano-proliferative (GN) (MPGN) and 8 had focal segmental glomerulosclerosis (FSGS). Median age at onset of disease and median time for CyA usage from disease onset was 22 months and 16 months respectively. Median duration of CyA therapy was 24 months (range 6-72) months. The data was analyzed to determine significance of variables on the outcome. Median follow up was 71 months (range 20-205) months. Eleven children were CyA resistant. Of the remaining 30 who were CyA responders, 22 (73.33%) were CyA dependent. Seven children developed chronic renal failure (CRF). CONCLUSIONS: The predictors for CyA non-responsiveness were steroid resistance, non MCNS on biopsy and longer duration between onset of nephrotic syndrome and CyA usage, irrespective of the age of onset of the disease. There was a higher incidence of CyA dependence among young responders. Patients with CyA resistance are at high risk for significant infections and CRF.